Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein

J. F. Trott, R. C. Hovey, S. Koduri, B. K. Vonderhaar

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Endocrine and autocrine prolactin (PRL) exerts effects on normal breast and breast cancer cells, and high serum PRL is a poor prognostic factor for colorectal cancer. Here we tested the hypothesis that short isoforms of the PRL receptor (PRLR) in human tissue regulate the actions of PRL in cancer. Using 3′ RACE we isolated five splice variants of the human PRLR (hPRLR), three of which encode the complete extracellular binding domain. Two of these isoforms, short form 1a (SF1a) and short form 1b (SF1b), possess unique intracellular domains encoded by splicing to exon 11 from exons 10 and 9 respectively. A third novel isoform (Δ7/11) reflects alternative splicing from exon 7 to exon 11 and encodes a secreted soluble PRL-binding protein. Additional splice variants of SF1b and Δ7/11 that lacked exon 4 (Δ4-SF1b and Δ4-Δ7/11) were also identified. Functional analyses indicated that hPRLR-SF1b is a strong dominant-negative to the differentiative function of the PRLR long form while hPRLR-SF1a is a weaker dominant-negative. Differential abundance of SF1a, SF1b and Δ7/11 expression was detected in normal breast, colon, placenta, kidney, liver, ovary and pancreas, and breast and colon tumors. Taken together, these data indicate the presence of multiple isoforms of the hPRLR that may function to modulate the endocrine and autocrine effects of PRL in normal human tissue and cancer.

Original languageEnglish (US)
Pages (from-to)31-47
Number of pages17
JournalJournal of Molecular Endocrinology
Volume30
Issue number1
DOIs
StatePublished - Feb 2003
Externally publishedYes

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Prolactin Receptors
Alternative Splicing
Exons
Protein Isoforms
Prolactin
Genes
Colon
Breast
Breast Neoplasms
Placenta
prolactin-binding protein
Pancreas
Colorectal Neoplasms
Ovary
Neoplasms
Kidney
Liver
Serum

ASJC Scopus subject areas

  • Endocrinology

Cite this

Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. / Trott, J. F.; Hovey, R. C.; Koduri, S.; Vonderhaar, B. K.

In: Journal of Molecular Endocrinology, Vol. 30, No. 1, 02.2003, p. 31-47.

Research output: Contribution to journalArticle

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